Gout is a disease caused by both congenital genetic (physical) and acquired dietary environment. If there is no genetic gout (not necessarily a family history of gout), it is not easy to cause gout by over-eating, but if there is excessive uric acid, the onset of gout can be reduced or avoided by dietary control, especially for those with a family history of gout and persistent high uric acid risk, they should start to develop good dietary habits from childhood. The best way to prevent the development of gout is through dietary control.
I. Treatment principles.
The treatment of gout should be based on different treatment plans for different periods.
1. Asymptomatic hyperuricemia period.
This is the key period to prevent and control acute gout attacks. In addition to diet control and alkalinization of urine, those with uric acid level >535μmon/L need to take long-term uric acid-lowering drugs to control uric acid in the normal range. In patients with hypertension, the use of antihypertensive drugs containing diuretics in relapsed formulations should be avoided.
2.Acute gouty arthritis attack period.
The main focus is on analgesia, and colchicine, non-steroidal anti-inflammatory and analgesic drugs or hormone therapy can be chosen. Within 28 days after an attack of gouty arthritis, the dose of urate-lowering drugs should not be activated or changed. Rapid fluctuation of uric acid (increase or decrease) during treatment can lead to aggravation of arthritis. A sudden drop in uric acid can lead to the release of crystals from the surface of gout stones, which can be phagocytosed by leukocytes and release chemokines that in turn attract more leukocytes to release lysosomal enzymes to destroy joints.
3. Interictal gout attack period.
The aim of treatment in this period is to keep serum uric acid in the normal range, prevent urate deposition in tissues and protect kidney function, while various triggering factors should be avoided. In addition to strict adherence to the principles of dietary therapy, uric acid-lowering drugs should be selected reasonably according to the kidney’s uric acid excretion capacity. In order to prevent acute arthritis induced by a sharp drop in blood uric acid, all kinds of uric acid-lowering drugs should be started from small doses and gradually increased to the effective therapeutic amount, and the drugs should be maintained for a long time after taking effect.
4. Chronic gouty stone arthritis period.
Analgesia and uric acid lowering are carried out simultaneously to prevent and protect the function of damaged organs. Surgery to correct deformed joints to improve their function.
Second, drug selection.
1.Colchicine
(1) Mechanism of action.
(1) Inhibition of chemotaxis, proliferation and phagocytosis of urate crystals by polymorphonuclear leukocytes.
(ii) Inhibition of lysosomal and lactic acid release.
(3) Raising the pH in the joint cavity and reducing the precipitation of urate crystals. However, it cannot reduce blood uric acid and does not increase uric acid excretion.
(2) Indications: Pain relief and prevention of acute gouty arthritis.
(3) Preparation and usage.
(1) In acute attacks: Colchicine 1.0mg for the first dose orally, 0.5mg after 1 hour, 0.5mg after 12 hours, 2-3 times daily.
②Prevention of acute gouty arthritis attacks: For acute attacks more than 3 times a year, it is recommended to take small doses of colchicine to prevent acute attacks. Colchicine 0.5mg twice a day. If the patient has no new gouty arthritis attacks for four months, reduce to once a day. If there is a new gouty attack, immediately increase to twice a day and so on.
(4) Side effects.
Gastrointestinal reactions such as abdominal pain, nausea, vomiting, and diarrhea often occur when symptoms are relieved. In severe cases, hemorrhagic gastroenteritis may occur. In a few cases, leukopenia, aplastic anemia, alopecia and myopathy can be caused by the use of the drug. Gastrointestinal symptoms such as diarrhea indicate that the dose is close to toxic and should be discontinued. Long-term use of the drug must be observed for blood picture, and is contraindicated in cases of low bone marrow function. The dosage should be reduced if there is liver or kidney disease. This drug can cause fertility deficits and should be avoided completely until the third month of pregnancy. In addition, it can enhance the effects of sedative, sleeping, analgesic and anesthetic drugs; it can also enhance the effects of amphetamine, epinephrine and ephedrine; reduce the effects of anticoagulants and anti-hypertensive drugs, so when used together, attention should be paid to the drug-related effects and adjust its dosage as appropriate.
(5) Precautions.
The drug is more effective when taken within 4 hours of an acute attack of gout, but its efficacy decreases if the attack lasts more than 24-48 hours. The effective therapeutic dose is close to the toxic dose, and close attention should be paid to gastrointestinal symptoms and prevention of drug toxicity.
2.Allopurinol
(1) Mechanism of action.
By competitively inhibiting xanthine oxidase, hypoxanthine cannot be oxidized to xanthine and yellow cannot be converted to uric acid. The clearance of hypoxanthine and xanthine by human kidney is higher than that of uric acid, and hypoxanthine is very easy to dissolve, so it does not cause damage to the kidney. After absorption, it is metabolized by the liver into isoxanthine, which is easily soluble in water, and excreted in the urine. The half-life of this drug is 1~3h. 1~2d after taking the drug, the serum uric acid starts to fall, and reaches the peak in 7~14d. Usually the serum uric acid drops to normal in 3~6 months.
(2) Indications.
(i) Those whose 24h uric acid excretion is still greater than 600mg (3054mmol) after treatment with low purine diet.
(ii) Those who are ineffective, allergic or intolerant to uric acid excreting drugs.
③ those with significantly reduced renal function and uric acid nephropathy or uric acid urinary tract stones.
④ before the start of chemotherapy or radiotherapy for lymphoproliferative or granuloproliferative diseases.
(5) Severe gritty gout with large urate accumulation and hyperuricemia.
(3) Contraindications: Those who have a history of allopurinol allergy.
(4) Dosage and Administration.
After 1 to 3 weeks, serum uric acid will be reduced to 178.4~297.4μmol/L (3~5mg/dl), urea nitrogen will be reduced and creatinine clearance will be normalized. The maintenance amount depends on the serum uric acid level and is usually 0.1 to 0.2g 2 to 3 times daily. Combination with uric acid-removing drugs can enhance the efficacy, but generally no combination is needed.
(5) Side effects.
The incidence of side effects is about 3% to 5%. Common side effects include.
(i) allergic rash, urticaria, drug fever, eosinophilia, etc.
② myelosuppressive leukopenia, hemolytic anemia.
(iii) Toxic hepatitis or transient glutathione transaminase elevation.
④Vasculitis and eye damage.
⑤ xanthine stones.
(6) Precautions.
It must be used only after the acute symptoms of gout are controlled. The first treatment should be started from a small dose, and patients should be informed to pay attention to the presence of rash and promptly seek medical consultation.
3.Benzbromarone
(1) Mechanism of action.
It is a benzofuran derivative, which is a pro-uric acid excretory drug. The mechanism of action is to inhibit the reabsorption of uric acid by the renal tubules, thus reducing the concentration of uric acid in the blood. Pharmacokinetics: 50mg is given orally to healthy adults, and the peak blood concentration is reached after about 2~3 hours, and the uric acid profile reaches the maximum in 4~5 hours.
(2) Indications: Simple primary hyperuricemia and non-acute attack of gouty arthritis.
(3) Contraindications.
(1) Those with moderate or severe renal impairment.
(ii) Those who have kidney stones.
(3) Pregnant and lactating women.
(4) Dosage.
Start with a small dose of 25mg (half tablet) a day and gradually increase to 100mg (2 tablets) a day without adverse reactions. Take after breakfast, and add 3g of sodium bicarbonate a day.
(5) Adverse reactions.
(1) Gastrointestinal reactions: nausea and abdominal discomfort, etc.
(2) Causes renal calculus and renal colic.
(3) Induced acute attack of arthritis.
④Rarely fever, rash and liver or kidney function impairment.
(6) Precautions.
① Drink more water and alkalize urine during administration. It is still effective for those with decreased renal function and blood creatinine greater than 130μ mol/L, but the daily urine volume must be maintained at more than 2000ml.
②Regular testing of renal function as well as changes in blood and urinary uric acid.
③The product must be applied only after the acute symptoms of gouty arthritis have been controlled.